1-16058636-C-A

Variant names:

• chr1-16058636-C-A
• rs1832151
• NM_182623.3:c.644G>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_182623.3(FAM131C):​c.644G>T​(p.Ser215Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.2 in 1,580,524 control chromosomes in the GnomAD database, including 5,151 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.22 (627 hom., cov: 44)
  • Exomes 𝑓: 0.20 (4524 hom.)
• Consequence: FAM131C NM_182623.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.457
• Publications: 16 publications found

Genes affected

FAM131C (HGNC:26717): (family with sequence similarity 131 member C)

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.005001545).
• BP6: Variant 1-16058636-C-A is Benign according to our data. Variant chr1-16058636-C-A is described in ClinVar as Benign. ClinVar VariationId is 1249070.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.327 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_182623.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM131C	NM_182623.3	MANE Select	c.644G>T	p.Ser215Ile	missense	Exon 7 of 7	NP_872429.2	Q96AQ9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM131C	ENST00000375662.5	TSL:1 MANE Select	c.644G>T	p.Ser215Ile	missense	Exon 7 of 7	ENSP00000364814.4	Q96AQ9
	FAM131C	ENST00000943020.1		c.608G>T	p.Ser203Ile	missense	Exon 6 of 6	ENSP00000613079.1
	FAM131C	ENST00000904375.1		c.461G>T	p.Ser154Ile	missense	Exon 6 of 6	ENSP00000574434.1

Frequencies

GnomAD3 genomes AF: 0.221 AC: 32800 AN: 148348 Hom.: 628 Cov.: 44

Gnomad AFR AF: 0.331

Gnomad AMI AF: 0.210

Gnomad AMR AF: 0.136

Gnomad ASJ AF: 0.211

Gnomad EAS AF: 0.00134

Gnomad SAS AF: 0.0977

Gnomad FIN AF: 0.233

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.202

Gnomad OTH AF: 0.188

GnomAD2 exomes AF: 0.170 AC: 37416 AN: 219784 AF XY: 0.169

Gnomad AFR exome AF: 0.340

Gnomad AMR exome AF: 0.0929

Gnomad ASJ exome AF: 0.196

Gnomad EAS exome AF: 0.000427

Gnomad FIN exome AF: 0.244

Gnomad NFE exome AF: 0.199

Gnomad OTH exome AF: 0.169

GnomAD4 exome AF: 0.198 AC: 283584 AN: 1432054 Hom.: 4524 Cov.: 103 AF XY: 0.195 AC XY: 138559 AN XY: 710232

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.345 AC: 11197 AN: 32418

American (AMR) AF: 0.102 AC: 4145 AN: 40618

Ashkenazi Jewish (ASJ) AF: 0.204 AC: 5186 AN: 25470

East Asian (EAS) AF: 0.000588 AC: 23 AN: 39104

South Asian (SAS) AF: 0.115 AC: 9406 AN: 82092

European-Finnish (FIN) AF: 0.241 AC: 12455 AN: 51760

Middle Eastern (MID) AF: 0.177 AC: 839 AN: 4736

European-Non Finnish (NFE) AF: 0.209 AC: 228892 AN: 1096534

Other (OTH) AF: 0.193 AC: 11441 AN: 59322

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.221 AC: 32838 AN: 148470 Hom.: 627 Cov.: 44 AF XY: 0.217 AC XY: 15744 AN XY: 72596

African (AFR) AF: 0.331 AC: 13002 AN: 39230

American (AMR) AF: 0.136 AC: 2049 AN: 15110

Ashkenazi Jewish (ASJ) AF: 0.211 AC: 725 AN: 3442

East Asian (EAS) AF: 0.00135 AC: 7 AN: 5194

South Asian (SAS) AF: 0.0975 AC: 467 AN: 4788

European-Finnish (FIN) AF: 0.233 AC: 2421 AN: 10374

Middle Eastern (MID) AF: 0.160 AC: 45 AN: 282

European-Non Finnish (NFE) AF: 0.202 AC: 13541 AN: 67066

Other (OTH) AF: 0.188 AC: 391 AN: 2080

Alfa AF: 0.219 Hom.: 993

ExAC AF: 0.152 AC: 18296

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.087
BayesDel_addAF	Benign	-0.75	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	18
DANN	Benign	0.93
DEOGEN2	Benign	0.0027	T
Eigen	Benign	-0.39
Eigen_PC	Benign	-0.29
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.63	T
MetaRNN	Benign	0.0050	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.46
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-0.97	N
REVEL	Benign	0.038
Sift	Uncertain	0.012	D
Sift4G	Benign	0.20	T
Polyphen		0.078	B
Vest4		0.045
MPC		0.57
ClinPred		0.0062	T
GERP RS		3.5
Varity_R		0.12
gMVP		0.20
Mutation Taster		=95/5	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.14		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1832151; hg19: chr1-16385131; COSMIC: COSV65152659; COSMIC: COSV65152659;